Premium
Suppression of integrin αυβ6 by RNA interference in colon cancer cells inhibits extracellular matrix degradation through the MAPK pathway
Author(s) -
Wang Jiayong,
Zhang Zhaoyang,
Xu Kesen,
Sun Xiaohui,
Yang Guangyun,
Niu Weibo,
Liu Enyu,
Peng Cheng,
Lin Pengfei,
Wang Jian,
Chen Rong,
Agrez Michael,
Niu Jun
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23656
Subject(s) - integrin , extracellular matrix , small hairpin rna , mapk/erk pathway , downregulation and upregulation , small interfering rna , microbiology and biotechnology , biology , cancer research , rna interference , phosphorylation , transfection , rna , cell , cell culture , biochemistry , gene , genetics
Integrin αυβ6 plays a very important role in the progression of colon cancer cells and is now defined as a novel, independent prognostic indicator for aggressive colon cancer in humans. Herein, we use the RNA interfering technology to downregulate the expression of αυβ6 in colon cancer cells. Our data demonstrate that plasmid vector based shRNA can effectively down‐regulate αυβ6 expression in protein and mRNA levels. Supression of integrin αυβ6 inhibits the phosphorylation and nonphosphorylation level of ERK1/2, the secretion of uPA, pro‐MMP‐9 and pro‐MMP‐2 in tumor conditioned medium, and more important, inhibits MAPK‐dependent [ 3 H] labeled collagen IV degradation via the plasminogen activation cascade. Our study demonstrates in vitro that supression of integrin αυβ6 inhibits extracellular matrix degradation through the MAPK pathway. © 2008 Wiley‐Liss, Inc.